Many clinical situations benefit from therapeutic regulation of the vascular, lymphatic or duct systems by restricting the flow of body fluid or secretions. The technique of embolization involves the therapeutic introduction of particles into the circulation to occlude vessels, for example, so as to either arrest or prevent hemorrhaging or to cut off blood flow to a structure or organ. Permanent or temporary occlusion of blood vessels is desirable for managing various diseases, disorders and conditions.
In a typical embolization procedure, local anesthesia is first given over a common artery. The artery is then percutaneously punctured and a catheter is inserted and fluoroscopically guided into the area of interest. An angiogram is then performed by injecting contrast agent through the catheter. An embolic agent is then deposited through the catheter. The embolic agent is chosen, for example, based on the size of the vessel to be occluded, the desired duration of occlusion, and/or the type of abnormality to be treated. A follow-up angiogram is usually performed to determine the specificity and completeness of the arterial occlusion.
Various polymer-based microspheres are currently employed to embolize blood vessels. These microspheres are usually introduced to the location of the intended embolization through microcatheters. Current commercially available embolic microspheres are composed of biostable polymers. The materials that have been most commonly used commercially include polyvinyl alcohol (PVA), acetalized PVA (e.g., Contour SETM embolic agent, Boston Scientific, Natick, Mass., USA) and crosslinked acrylic hydrogels (e.g., Embospheres®, Biosphere Medical, Rockland, Mass., USA). Similar devices have been used in chemoembolization to increase the residence time of the therapeutic after delivery. In one specific instance, a therapeutic agent (doxorubicin) has been directly added to polyvinyl alcohol hydrogel microspheres such that it can be released locally after delivery (e.g., DC Bead™ drug delivery chemoembolization system, Biocompatibles International plc, Farnham, Surrey, UK).
Current commercial processes for the production of embolic particles include emulsion polymerization as well as emulsification of preformed polymers and encapsulation technologies. For example microspheres of PVA can be prepared by dispersing an aqueous PVA solution in an immiscible solvent and crosslinking it with a suitable material such as an aldehyde (e.g., formaldehyde or gluteraldehyde). Another example of microsphere preparation involves dropping an aqueous solution of PVA and sodium alginate into a calcium chloride bath, followed by reaction with an aldehyde to crosslink the PVA. See, e.g., Pub. No. US 2003/0185895 to Lanphere et al.
It is also known to use polymer-based microspheres as augmentative materials for aesthetic improvement, including improvement of skin contour. Furthermore, polymer-based microspheres have also been used as augmentative materials in the treatment of various diseases, disorders and conditions, including urinary incontinence, vesicourethral reflux, fecal incontinence, intrinsic sphincter deficiency (ISD) and gastro-esophageal reflux disease. For instance, a common method for treating patients with urinary incontinence is via periurethral or transperineal injection of a bulking agent that contains polymer-based microspheres. In this regard, methods of injecting bulking agents commonly require the placement of a needle at a suitable treatment region, for example, periurethrally or transperineally. The bulking agent is injected into a plurality of locations, assisted by visual aids, causing the urethral lining to coapt. In some cases additional applications of bulking agent are required.